CDC42-Enhanced T Cell Migration for Solid Tumors
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Solution Overview
Problem
Current CAR-T therapy is ineffective for treating solid tumor cancers due to the inability of CAR-T cells to effectively migrate towards and target cancer cells throughout the body.
Innovation Solution
Modification of T cells to enhance the expression and function of CDC42, leading to increased cytokine release, such as IFNγ and Granzyme B, and improved migration capability in response to chemokines, thereby enhancing their ability to target and eliminate cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-T cells are used to treat solid tumor cancers, then cancer treatment is attempted, but the CAR-T cells fail to migrate effectively towards cancer cells spreading over the body
Solution Approach 1:
The patent enhances the migration capability of CAR-T cells by modifying the expression level of CDC42 protein. This parameter change in protein expression directly improves the migratory speed and effectiveness of T cells toward cancer cells, resolving the contradiction between treatment reliability and migration speed.
2Reliability
If CDC42 expression is enhanced in T cells, then migration capability and cytokine release are improved, but the complexity of cell modification increases
Solution Approach 1:
The patent employs parameter changes by adjusting the expression level of a single endogenous gene (CDC42) rather than introducing complex external systems. This approach improves migration capability while minimizing modification complexity, as it relies on regulating existing cellular machinery rather than adding foreign genetic elements.
Data Source
AI summary
Embodiments relate to a modified T cell comprising an antigen binding molecule, wherein expression and/or function of CDC42 in the modified cell has been enhanced. In embodiments, the modified cell has an increased level of cytokine release in response to an antigen that the antigen binding molecule binds as compared to a corresponding T cell that does not overexpress CDC42. In embodiments, the cytokine release comprises a cytokine release of IFNγ. In embodiments, the modified cell has an enhanced migration capability in response to a chemokine as compared to a corresponding T cell that does not overexpress CDC42.